Receptor-targeting phthalocyanine photosensitizer for improving antitumor photocytotoxicity.
Receptor-targeting phthalocyanine photosensitizer for improving antitumor photocytotoxicity.
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靶向受体的酞菁光敏剂可提高抗肿瘤光细胞毒性
DOI：
10.1371/journal.pone.0037051
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Huang M
中科院分区：
文献类型：
--
作者：
Xu P;Chen J;Chen Z;Zhou S;Hu P;Chen X;Huang M
光动力学疗法（PDT）是一种很有前途的治疗方式，其使用光敏剂捕获可见光，从而在照射区域产生光毒性。PDT已用于许多病理适应症，包括肿瘤。光敏剂的一个关键的理想特征是对肿瘤细胞的高光毒性，但对正常细胞没有。在这项研究中，我们共轭促性腺激素释放激素（GnRH）的光敏剂，酞菁锌（ZnPc），以提高其特异性乳腺癌，其中过表达GnRH受体。酞菁锌与其他光敏剂相比具有独特的优点，但作为单一异构体难以衍生化和纯化。我们以前开发了一种直接的方法来合成单取代的β-羧基酞菁锌（ZnPc-COOH）。评价了该ZnPc-GnRH缀合物的光物理和光化学参数，包括荧光量子产率（λ f）、荧光衰减时间（τs）和单线态氧量子产率（λ Δ），发现其与ZnPc的相当，表明添加GnRH肽不会显著改变ZnPc的单线态氧的产生。测试了该缀合物的细胞摄取和光毒性，发现与具有低水平GnRH受体的细胞如人胚肺成纤维细胞（HELF）和人肝癌（HepG 2）细胞相比，在过表达GnRH受体的人乳腺癌细胞系（MDA-MB-231和MCF-7细胞）上显著增强。此外，发现GnRH受体阻断剂Cetrorelix明显减轻了MCF-7细胞对该缀合物的细胞摄取，表明该缀合物的细胞摄取是GnRH受体介导的。总之，这些发现表明，将ZnPc与GnRH类似物偶联是提高ZnPc对GnRH受体过表达的肿瘤的选择性的有效方法。
Photodynamic therapy (PDT) is a promising therapeutic modality which uses a photosensitizer to capture visible light resulting in phototoxicity in the irradiated region. PDT has been used in a number of pathological indications, including tumor. A key desirable feature of the photosensitizer is the high phototoxicity on tumor cells but not on normal cells. In this study, we conjugate a gonadotropin-releasing hormone (GnRH) to a photosensitizer, Zinc phthalocyanine (ZnPc), in order to enhance its specificity to breast cancer, which over-expresses GnRH receptor. ZnPc has unique advantages over other photosensitizers, but is difficult to derivatize and purify as a single isomer. We previously developed a straight-forward way to synthesize mono-substituted β-carboxy-phthalocyanine zinc (ZnPc-COOH). Photophysical and photochemical parameters of this ZnPc-GnRH conjugate including fluorescence quantum yield (Фf), fluorescence decay time (τs) and singlet oxygen quantum yield (ФΔ) were evaluated and found comparable with that of ZnPc, indicating that addition of a GnRH peptide does not significantly alter the generation of singlet oxygen from ZnPc. Cellular uptakes and phototoxicities of this conjugate were tested and found significantly enhanced on human breast cancer cell lines overexpressing GnRH receptors (MDA-MB-231 and MCF-7 cells) compared to cells with low levels of GnRH receptors, such as human embryonic lung fibroblast (HELF) and human liver carcinoma (HepG2) cells. In addition, the cellular uptake of this conjugate toward MCF-7 cells were found clearly alleviated by a GnRH receptor blocker Cetrorelix, suggesting that the cellular uptake of this conjugate was GnRH receptor-mediated. Put together, these findings revealed that coupling ZnPc with GnRH analogue was an effective way to improve the selectivity of ZnPc towards tumors with over-expressed GnRH receptors.
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影响因子：
4.1
作者：
KAKAR, SS;GRIZZLE, WE;NEILL, JD
通讯作者：
NEILL, JD
影响因子：
3.2
作者：
Bai, Ming;Lo, Pui-Chi;Ng, Dennis K. P.
通讯作者：
Ng, Dennis K. P.
影响因子：
5.8
作者：
EIDNE, KA;FLANAGAN, CA;MILLAR, RP
通讯作者：
MILLAR, RP
DOI：
10.1007/978-0-387-74911-2_32
发表时间：
2008-01-01
期刊：
OXYGEN TRANSPORT TO TISSUE XXIX
影响因子：
--
作者：
Kakar, S. S.;Jin, H.;Kang, Kyung A.
通讯作者：
Kang, Kyung A.
影响因子：
3.3
作者：
Carcenac, M;Larroque, C;Pèlegrin, A
通讯作者：
Pèlegrin, A